Secretory IgA-mediated basophil activation. Its mechanisms and implication in allergy.

分泌型IgA(SIgA)是上呼吸道和下呼吸道粘膜分泌物中含量最丰富的Ig亚型，嗜碱性粒细胞在变态反应性炎症中发挥效应作用。我们最近证明，将SIgA固定在琼脂糖珠上能够诱导嗜碱性粒细胞脱颗粒(约占总组胺的15%)。为了研究这种脱颗粒的详细机制，我们在本研究中建立了一种新的SIgA介导的嗜碱性细胞激活的检测系统。将SIgA固定在塑料表面可引起相当于抗IgE抗体的强组胺释放(约占总组胺的50%)，并用不同的抑制剂分析了SIgA对嗜碱性粒细胞信号转导的性质。百日咳毒素可完全抑制SIgA诱导的嗜碱性粒细胞组胺释放，但不影响抗IgE诱导的释放。磷脂酰肌醇3-激酶(PI-3-Kinase)抑制剂Wortmannin也能抑制SIgA介导的释放。这些结果强烈地表明，SIgA通过一种不依赖于IgE的新机制激活嗜碱性粒细胞，该机制涉及Gi蛋白和PI3-激酶。

Secretory IgA (sIgA) is the most abundant Ig isotype in mucous secretions in the upper and lower airways, where basophils exert effector functions during allergic inflammation. We recently demonstrated that immobilized sIgA on Sepharose beads is capable of inducing basophil degranulation (〜15% of total histamine). To investigate the detailed mechanisms of this degranulation, we established in this study a new assay system for sIgA-mediated basophil activation. Immobilized sIgA on a plastic surface induced strong histamine release (〜50% of total histamine) comparable to anti-IgE, and we analyzed the nature of basophil signal transduction by sIgA using various inhibitors. sIgA-induced basophil histamine release was inhibited completely by pertussis toxin, but anti-IgE-induced release was not affected. sIgA-mediated release was also inhibited by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, wortmannin. These results strongly suggest that sIgA activates basophils via an IgE-independent novel mechanism involving both Gi protein and PI 3-kinase.